The project is designed to elucidate the role of xenobiotic-metabolizing enzymes in skin as mediators of the toxicity of environmental agents. Mixed-function oxidases, (including aryl hydrocarbon hydroxylase), glutathione S-transferase, UDP-glucuronosyltransferase and sulfotransferase activities are measured in whole skin, epidermal cells or subcellular fractions of epidermal cells from hairless mice (Hrs/J). Mixed-function oxidase activities in Zymbal's glands from mice and rats were compared with those in skin sebaceous cells. Epidermal cell types high in xenobiotic metabolizing activity and/or cytochrome P-450 content are being identified. Changes in xenobiotic metabolism and/or in the content of mixed-function oxidase components after exposure (topical or systemic) of mice to various effectors such as polycyclic hydrocarbons and steroids are being investigated. Metabolism of endogeneous substrates by various skin cell fractions is being studied -- e.g. -- steroids, prostaglandins and leukotrienes.